Glioblastoma Multiforme of Brain Clinical Trial
Official title:
A Phase 1b Study to Evaluate CHM-1101, a CAR T-Cell Therapy With a Chlorotoxin Tumor-Targeting Domain for Patients With Matrix Metallopeptidase 2 Positive (MMP2+) Recurrent or Progressive Glioblastoma Multiforme
This is a phase 1b study to evaluate the safety of chimeric antigen receptor (CAR) T cells with a chlorotoxin tumor-targeting domain (ie, CHM-1101, the study treatment) to determine the best dose of CHM-1101, and to assess the effectiveness of CHM-1101 in treating MMP2+ glioblastoma that has come back (recurrent) or that is growing, spreading, or getting worse (progressive).
Status | Recruiting |
Enrollment | 42 |
Est. completion date | January 2041 |
Est. primary completion date | October 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Documented informed consent of the subject and/or legally authorized representative. - Agreement to allow the use of archival tissue from diagnostic tumor biopsies. - Age 18 years and older. - ECOG status of 0 or 1. - Life expectancy =12 weeks. - Subject has a prior histologically confirmed diagnosis of a grade 4 glioblastoma multiforme (GBM) or a prior histologically confirmed diagnosis of a grade 2 or 3 malignant glioma and now has radiographic progression consistent with a grade 4 GBM (IDH wild type), grade 4 diffuse astrocytoma (IDH mutant), or has a unifocal relapse of GBM. - Relapsed disease: radiographic evidence of recurrence/progression of measurable disease after standard therapy and = 12 weeks after completion of front-line radiation therapy. - Confirmed MMP2+ tumor expression by IHC (=20% moderate/high MMP2 score [2+ or 3+]). - Adequate venous access to perform leukapheresis. - No known contraindications to leukapheresis or steroids. - In-range baseline laboratory values for WBC (>2000/dL [or ANC =1000/mm^3]), platelets (=75000/mm^3), total bilirubin (=1.5xULN), AST (=2.5xULN), ALT (=2.5xULN), serum creatinine (=1.5xmg/dL), and oxygen saturation (=95% on room air) - Seronegative for human immunodeficiency virus (HIV) by antigen/antibody (Ag/Ab) testing. - Seronegative for hepatitis B and/or hepatitis C virus. - Women of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required. - Agreement by women AND men of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of CHM-1101. (Childbearing potential is defined as not being surgically sterilized (women and men) or, for women, having not been free from menses for > 1 year.) Exclusion Criteria: - Within 3 months of having received prior bevacizumab therapy at the time of enrollment. - Not yet recovered from toxicities of prior therapy. - Uncontrolled seizure activity and/or clinically evident progressive encephalopathy. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent. - Clinically significant uncontrolled illness. - Active infection requiring antibiotics. - Known history of HIV or hepatitis B or hepatitis C infection. - Other active malignancy. - Women only-pregnant or breastfeeding. - Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures. - Prospective subjects who, in the opinion of the Investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics). |
Country | Name | City | State |
---|---|---|---|
United States | St. David's South Austin Medical Center - Sarah Cannon - Austin | Austin | Texas |
United States | City of Hope Medical Center | Duarte | California |
Lead Sponsor | Collaborator |
---|---|
Chimeric Therapeutics |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Dose-limiting toxicity (DLT) | Assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. | 28 days | |
Primary | Cytokine Release Syndrome (CRS) | Assessed per American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading guideline, evaluating levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry). | up tp 15 years | |
Primary | All other adverse events and toxicities | Assessed per NCI CTCAE v5.0. | up to 15 years | |
Secondary | Chimeric antigen receptor (CAR) T cell | Assess levels and phenotype detected in tumor cyst fluid (TCF), peripheral blood (PB), and cerebrospinal fluid (CSF) (absolute number per µL by flowcytometry). | up to 15 years | |
Secondary | Endogenous T cell | Assess level and phenotype detected in TCF, PB, and CSF (absolute number per µL by flowcytometry). | up to15 years | |
Secondary | Human anti-CAR antibody (HACA) | Serum samples will be evaluated for HACA against the CLTX(EQ)28? therapeutic agent. | up to 15 years | |
Secondary | Progression free survival (PFS) time | Measured from the date of first infusion of CAR-T cells until the first date when progressive disease (PD) is objectively documented or death from any cause, whichever is earlier. | 12 months | |
Secondary | Overall survival (OS) | Measured from the date of first infusion of CAR-T cells until death. | up to 15 years | |
Secondary | Disease response | Assessed by modified Response Assessment in Neuro-Oncology Criteria (RANO) criteria. | 12 months | |
Secondary | Clinical benefit rate | The proportion of participants who experience a complete response, a partial response, or stable disease that is 3 months or greater in duration. | 12 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT03657576 -
Trial of C134 in Patients With Recurrent GBM
|
Phase 1 | |
Recruiting |
NCT05685004 -
Study of Neoantigen-specific Adoptive T Cell Therapy for Newly Diagnosed MGMT Negative Glioblastoma Multiforme (GBM)
|
Phase 2/Phase 3 | |
Recruiting |
NCT05076513 -
Trial of Niraparib in Participants With Newly-diagnosed Glioblastoma and Recurrent Glioma
|
Early Phase 1 | |
Active, not recruiting |
NCT03665545 -
Pembrolizumab in Association With the IMA950/Poly-ICLC for Relapsing Glioblastoma
|
Phase 1/Phase 2 | |
Completed |
NCT02474966 -
Effect of Deep TMS on the Permeability of the BBB in Patients With Glioblastoma Multiforme: a Pilot Study
|
Phase 2 | |
Active, not recruiting |
NCT02137759 -
MRSI to Predict Response to RT/TMZ ± Belinostat in GBM
|
Phase 2 | |
Enrolling by invitation |
NCT03170141 -
Immunogene-modified T (IgT) Cells Against Glioblastoma Multiforme
|
Phase 1 | |
Recruiting |
NCT04842513 -
Multi Peptide Vaccination With XS15 in Addition to Standard Postoperative Radiation Therapy and Temozolomide Chemotherapy in Newly Diagnosed Glioblastoma
|
Phase 1 | |
Recruiting |
NCT04869449 -
Neuro-pharmacological Properties of Repurposed Ketoconazole in Glioblastomas
|
Early Phase 1 | |
Recruiting |
NCT03633552 -
Efficacy of Two Temozolomide Regimens in Adjuvant Treatment of Patients With Brain High Grade Glioma
|
Phase 3 | |
Not yet recruiting |
NCT05095441 -
A Clinical Study of Intratumoral MVR-C5252 (C5252) in Patients With Recurrent or Progressive Glioblastoma
|
Phase 1 | |
Completed |
NCT00003456 -
Antineoplaston Therapy in Treating Patients With Newly-diagnosed Glioblastoma Multiforme
|
Phase 2 | |
Completed |
NCT03047473 -
Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme
|
Phase 2 | |
Enrolling by invitation |
NCT05116137 -
The Impact of Resistance ExerciSe on Muscle Mass in GlioblaSToma Survivors
|
N/A | |
Active, not recruiting |
NCT04968366 -
Safety & Efficacy of DC Vaccine and TMZ for the Treatment of Newly-diagnosed Glioblastoma After Surgery
|
Phase 1 | |
Suspended |
NCT04222309 -
Laparoscopically Harvested Omental Free Tissue Autograft to Bypass the Blood Brain Barrier (BBB) in Human Recurrent Glioblastoma Multiforme (rGBM)
|
Phase 1 | |
Not yet recruiting |
NCT06186440 -
Cisplatin Plus Temozolomide Compared With Temozolomide in Patients With MGMT Promotor Unmethylated Glioblastoma
|
Phase 1/Phase 2 | |
Recruiting |
NCT06283927 -
The RECSUR-study: Resection Versus Best Oncological Treatment for Recurrent Glioblastoma (ENCRAM 2302)
|
||
Recruiting |
NCT06273176 -
The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma
|
||
Recruiting |
NCT06146725 -
The RESBIOP-study: Resection Versus Biopsy in High-grade Glioma Patients (ENCRAM 2202)
|